Two-year results of tapered dupilumab for CRSwNP demonstrates enduring efficacy established in the first 6 months.

BACKGROUND: Dupilumab is an anti-T2-inflammatory biological registered for chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), indicated by integrated CRS-care pathways when optimal medico-surgical treatment yields insufficient CRS control. This study aims to evaluate long-term results with focus on established therapeutic efficacy while tapering dupilumab. METHODS: Real-life, prospective observational cohort study in single tertiary referral center with add-on dupilumab as primary biological treatment in adult (≥18 years) biological-naïve CRSwNP patients per the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS)2020-indication with a 2-year follow-up. Tapering (increasing interdose interval) applied every 24 weeks, conditional to sufficient treatment response and CRS control. RESULTS: Mean scores (s.d.) of all co-primary outcomes improved significantly from baseline ( 228) to the 48 ( 214) and 96-weeks ( 99) timepoints: Nasal Polyp Score (0-8) improved from 5,3 (1,9) to 1,4 (1,8) and 1,3 (1,7); SinoNasal Outcome Test (SNOT)-22 (0-110) improved from 53,6 (19,6) to 20,2 (15,4) and 21,2 (15,6); Sniffin'Sticks-12 identification test (0-12; 0-6 anosmia, 7-10 hyposmia, 11-12 normosmia) improved from 3,7 (2,4) to 7,7 (2,9) and 7,3 (3,04); Asthma Control Test (5-25; >19 indicating well-controlled asthma) improved from 18,5 (4,8) to 21,8 (3,8) and 21,4 (3,9). Tapering was feasible in 79,5% of the patients at the 24-weeks timepoint, and in 93,7% and 95,8% at the 48- and 96-weeks timepoints, respectively. One-way repeated-measures ANOVA demonstrated no significant alterations of individual co-primary outcome mean-scores from 24 weeks onward. CONCLUSION: This first long-term real-life prospective observational cohort study shows high therapeutic efficacy of dupilumab for severe CRswNP in the first 2 years. Therapeutic efficacy is principally established within 24 weeks and endures while tapering dupilumab conditional to treatment response and CRS control.

Evaluation of switching or simultaneous use of biologic treatment in patients with severe chronic rhinosinusitis with nasal polyps and severe asthma. Considerations in clinical decision making.

INTRODUCTION: Type 2 targeting biologics have reached the market first for asthma and since 2019 also for CRSwNP. As clear guidelines and predictors for optimal biological choice are missing, patients are sometimes required to switch biologic therapy in order to find the optimal treatment result. In this paper, we evaluate reasons for switching biologics and the treatment effects after each sequential switch. MATERIALS AND METHODS: Ninety-four patients who switched from one biologic to another for their treatment of CRSwNP and asthma were evaluated. RESULTS: Twenty patients experienced satisfactory control of CRSwNP, but insufficient control of severe asthma. Fifty-one patients experienced satisfactory control of severe asthma, but insufficient control of CRSwNP/EOM. Twenty-eight patients experienced insufficient control of both upper and lower airways. Thirteen patients had to switch because of side effects. Furthermore, two cases are described to clarify clinical decision-making. DISCUSSION: For abovementioned patients, a multidisciplinary approach is mandatory to find the best suitable biologic. It seems ineffective to switch to a second anti-IL5 treatment if the first one is not successful. Most patients that failed omalizumab and/or an anti-IL-5 treatment are well controlled on dupilumab. Therefore, we suggest to use dupilumab as first choice when switching biologic agents.

Chronic Rhinosinusitis Outcome Registry (CHRINOSOR): Establishment of an International Outcome Registry Driven by mHealth Technology.

BACKGROUND: Real-world evidence (RWE) is a valuable instrument to better understand the patient journey and effectiveness of therapies. RWE on the prevalence of uncontrolled chronic rhinosinusitis (CRS) and CRS natural course of disease across Europe is scarce. In addition, there is limited RWE that enables comparison of the effectiveness of marketed therapies including topical or systemic corticosteroids, sinus surgery, or biologics. OBJECTIVE: To establish an international CHRonic rhINOSinusitis Outcome Registry (CHRINOSOR) based on real-world data collection enabled by mobile health technology. METHODOLOGY: A digital platform, Galenus Health, supporting patients and physicians in the management of chronic respiratory diseases, is used to collect data on patient profile, disease history, patient outcomes, and a set of relevant clinical outcomes. Adult patients with a diagnosis of CRS are eligible for inclusion. RESULTS: A collaborative scientific network of 17 university ear-nose-throat (ENT) clinics from 10 European countries has been established with the aim to collect real-world data in a longitudinal and standardized manner. The Galenus Health digital platform is currently being implemented in these ENT clinics taking into account legal, privacy, and data security aspects. Up to 300 patients have already been included. CONCLUSIONS: CHRINOSOR is a collaborative effort that aims at improving our understanding of CRS, its comorbidities, and the effectiveness of its treatments. Ultimately, these insights will guide us as scientific community to develop future care pathways informed by RWE.

Biologicals and Endoscopic Sinus Surgery for Severe Uncontrolled Chronic Rhinosinusitis With Nasal Polyps: An Economic Perspective.

Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is a chronic disease with a high prevalence and high disease burden, and the lack of a cure. The socioeconomic burden of the disease is substantial and has been disproportionally increasing over past decades. Treatment is aimed at attaining disease control. Traditionally, topical corticosteroids, endoscopic sinus surgery, and oral corticosteroids are used to treat CRSwNP. The advent of biologics has revolutionized CRSwNP treatment, but these drugs are expensive. From an economic standpoint, it is worth debating whether biologics should be employed in patients with severe uncontrolled CRSwNP who fail to attain disease control with current therapies. This clinical commentary review provides an overview of the socioeconomic burden of chronic rhinosinusitis and treatment modalities, compares endoscopic sinus surgery versus biologics for severe CRSwNP, discusses management recommendations, and highlights future needs in this field. New ways to reduce costs of biologic treatments need to be explored to attain cost-effectiveness and provide patients who have severe CRSwNP with adequate treatment.

Dupilumab for the treatment of chronic rhinosinusitis with nasal polyposis.

Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) affects 1-2.5% of the population and is associated with significant adverse effects on quality of life (QoL). CRSwNP is strongly correlated with (late onset) asthma with 30-70% of the CRSwNP patients having asthma. Health-care spending in rhinosinusitis is high, especially because of indirect costs.Areas covered: In the last years, the recognition of endotyping as an essential presumption to precision medicine has significantly changed the integrated care pathways in the treatment of chronic rhinosinusitis. Dupilumab is the first biological available for the treatment of CRswNP, since late 2019. Treatment with dupilumab results in a significant improvement of QoL (measured as SNOT-22), rhinosinusitis disease severity, symptoms of rhinosinusitis, and especially sense of smell, nasal polyp score, Lund-Mackay CT score, and asthma outcomes (ACQ5 and FEV1) compared to placebo.Expert opinion: At this moment, the high cost of the treatment requires careful patient selection and within the EUFOREA and EPOS2020 context, experts have tried to give guidance based on today's data. We now need trials evaluating which patients benefit most from treatment with biologicals and in which patients the treatment is cost-effective.

Therapeutic Options for Chronic Rhinosinusitis in N-ERD Patients.

Patients with non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) often suffer from chronic rhinosinusitis (CRS) with nasal polyps, a form of primary diffuse Type 2 CRS. Although this disease is also seen in NSAID-tolerant patients, CRS in N-ERD often is more severe and more treatment resistant; local nasal therapy (nasal corticosteroids) and endoscopic sinus surgery are employed like in NSAID-tolerant patients, but with limited and/or short-lived effects. This mini-review gives an overview of the current additional treatment options for CRS in N-ERD. As such diets, aspirin therapy after desensitization, antileukotriene therapy and biologicals are discussed based on the current body of literature. Selecting the right treatment strategy depends on shared-decision making, local availability and cooperation between ENT-surgeons, allergists, and pulmonologists.

Complete Remission of Severe Eosinophilic Otitis Media With Dupilumab: A Case Report.

Eosinophilic otitis media (EOM) is a difficult-to-treat otitis media (OM) characterized by eosinophilic accumulation in the middle ear mucosa and secretion. Associated sensorineural hearing loss can eventually lead to (functional) deafness. EOM is strongly associated with type 2 inflammation driven respiratory disease, i.e. asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), for which biological treatment is available. This case report discusses a patient suffering from EOM with severe mixed hearing loss, nearing functional deafness. Dupilumab treatment resulted in complete and enduring remission of the EOM, enabling adequate hearing rehabilitation. Concurrent control of the comorbid asthma and CRSwNP was obtained. Laryngoscope, 131:2649-2651, 2021.

Neuroendocrine neoplasms of the middle ear: Unpredictable tumor behavior and tendency for recurrence.

BACKGROUND: Middle ear adenomatous neuroendocrine tumors (MEANTs) are rare temporal bone tumors. This study evaluates its clinical behavior and therapy outcome. METHOD: Retrospective case review in a tertiary referral center evaluating histopathology, immunohistochemistry, treatment, and outcome. RESULTS: Nine patients were diagnosed with MEANT. One patient presented with locally invasive tumor and underwent extensive en-bloc tumor resection with adjuvant radiotherapy. Seven of eight patients with locally non-aggressive tumor confined to the tympanomastoid space underwent tumor resection. Two patients were disease-free, five presented recurrence, even after apparent successful surgery. All tumors showed neuroendocrine features. Histopathology and immunohistochemistry did not yield prognostic tumor characteristics. CONCLUSION: MEANTs are rare tumors with uncertain biological behavior and subsequent unpredictable clinical course. The preferred treatment is complete surgical tumor resection. They have a high tendency for recurrence, irrespective of negative intermediary surgery. As of yet, there are no prognostic biomarkers, including histopathology and immunohistochemistry.

Surgical Treatment of Chronic Parotitis.

Introduction chronic parotitis (CP) is a hindering, recurring inflammatory ailment that eventually leads to the destruction of the parotid gland. When conservative measures and sialendoscopy fail, parotidectomy can be indicated. Objective to evaluate the efficacy and safety of parotidectomy as a treatment for CP unresponsive to conservative therapy, and to compare superficial and near-total parotidectomy (SP and NTP). Methods retrospective consecutive case series of patients who underwent parotidectomy for CP between January 1999 and May 2012. The primary outcome variables were recurrence, patient contentment, transient and permanent facial nerve palsy and Frey syndrome. The categorical variables were analyzed using the two-sided Fisher exact test. Alongside, an elaborate review of the current literature was conducted. Results a total of 46 parotidectomies were performed on 37 patients with CP. Near-total parotidectomy was performed in 41 and SP in 5 cases. Eighty-four percent of patients was available for the telephone questionnaire (31 patients, 40 parotidectomies) with a mean follow-up period of 6,2 years. Treatment was successful in 40/46 parotidectomies (87%) and 95% of the patients were content with the result. The incidence of permanent and transient facial nerve palsy was 0 (0%) and 12 (26.1%), respectively. Frey syndrome manifested in 20 (43.5%) patients. Neither this study nor careful review of the current literature resulted in evident difference between SP and NTP regarding the primary outcome variables. Conclusion parotidectomy is a safe and effective treatment for CP in case conservative therapy fails. There is no evidence of a distinct difference between SP and NTP regarding efficiency, facial nerve palsy or Frey syndrome.